Siva Karthik Varanasi, PhD
By Caleb White | Date published: May 15, 2025
May Researcher Spotlight: Siva Karthik Varanasi, PhD
In this month’s Researcher Spotlight, we feature the work of Siva Karthik Varanasi, PhD, assistant professor of medicine in the Division of Innate Immunity and a faculty member in the Program in Innate Immunity. Dr. Varanasi’s lab aims to understand the molecular mechanisms of tissue-specific immune responses. In particular, he studies how tissue-infiltrating T cells metabolically adapt to maintain optimal responses and how these adaptations are dysregulated in disease.
After completing his Master’s in biotechnology, Dr. Varanasi was initially interested in researching next-generation sequencing and whole-genome sequencing. While pursuing a PhD in genome science and technology, however, he discovered a newfound passion for immunology through the help of his mentor, Dr. Barry Rouse, whose lab was studying regulatory T cells and the role they play in virus infections. Dr. Varanasi decided to pivot to studying viral immunology, and after completing his PhD he became a postdoctoral research associate at the Salk Institute for Biological Sciences in San Diego, California, where he worked with Dr. Susan Kaech to evaluate T cell responses in different cancer models.
“During this time I wanted to expand the scope of my research into two areas that I was unfamiliar with – translational research and innate immunity,” Dr. Varanasi said. “I wanted to know how I could translate my findings into the clinic and impact patients’ lives. I also wanted to learn how T cells interact with macrophages and myeloid cells and how that dictates a patient’s response to cancer or infectious diseases. UMass has extraordinary programs and faculty in both of these areas, and I’m honored to have them as my colleagues.”
Dr. Varanasi’s lab includes several areas of research. His postdoctoral work ended with a major observation that T cells in liver cancer are influenced by bile acids that accumulate in the liver, which are then affected in two possible ways. One way is being influenced for survival, where the bile acids kill the T cells. The other way is being influenced at a functional level, where the bile acids, particularly the ones that come from the gut microbiome, influence T cell functionality. One of his current projects is studying how the concept of bile acid influencing T cell responses affects non-cancerous diseases (such as autoimmune diseases) in the liver. “With our mouse models, we can tease apart how bile acids contribute to diseases inside and outside the liver such as the heart and brain,” noted Dr. Varanasi.
Another project is studying how T cells spatially adapt to the liver. Metabolic pathways in the liver are spatially distributed – for example, cholesterol biosynthesis occurs in certain regions of the liver, while fatty acid oxidation or amino acid synthesis happens on the other side of the liver. Dr. Varanasi’s goal is to analyze how the functionality of T cells is affected depending on which niche of the liver they are in.
“Overall, this is an exciting area of research that I'm very interested in,” he said. “The information we gather may be further used to manipulate T cell responses and manage a variety of diseases where they are involved.”
Dr. Varanasi received his MSc in Biotechnology from the Vellore Institute of Technology in India in 2011 and his PhD from the University of Tennessee, Knoxville in 2018. He joined the Division of Innate Immunity at UMass Chan Medical School in the Fall of 2024.
We are thrilled Dr. Varanasi has joined us in the Department of Medicine!